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Indian Pediatr 2012;49: 668-670
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Chronic Myeloid Leukemia in a Child with IgA
Nephropathy
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Amish Udani, Vijayakumar Mahalingam, Prahlad Nageswaran and *Sudha
Ekambaram
From the Department of Pediatric Nephrology and
*Pediatrics, Mehta Children’s Hospitals, Chennai, India.
Correspondence to: Dr M Vijayakumar, Consultant
Pediatric Nephrologist, Mehta Children’s Hospitals, No.2(e) Mc Nichols
Road, 3rd Lane, Chetput, Chennai 600 031, Tamilnadu, India.
Email: [email protected]
Received: September 5, 2011;
Initial review: September 30, 2011;
Accepted: February 27, 2012.
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We report an 11 year old boy with IgA nephropathy developing chronic
myeloid leukemia on follow-up. This association suggests that a B cell
defect might be involved in the pathogenesis of these two conditions.
Key words: Chronic myeloid leukemia, IgA nephropathy.
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There is increasing evidence of abnormal
glycosylation of immunoglobulin A1 (IgA1) subclass due to B-cell
defect in the pathogenesis of immune-complex mediated IgA
nephropathy [1]. The occurrence of IgA nephropathy and leukemia has
been reported rarely in children [2]. Here we report a child
with IgA nephropathy developing chronic myeloid leukemia (CML) on
follow-up.
Case Report
An 11-yr-old boy was diagnosed acute nephritic
syndrome at 3 year back in view of hypertension, hematuria,
proteinuria (spot urine protein to creatinine ratio 0.75), mild
renal insufficiency (serum creatinine 1.1 mg/dL), and normal serum
albumin and cholesterol. He had no anemia, leukocytosis or
electrolyte disturbances. He was treated with salt and fluid
restriction and oral nifedepine for hypertension. Serum complement
C3 level was normal, anti nuclear antibody and anti double standard
DNA was negative. In view of persistent hypertension, renal
insufficiency, microscopic hematuria and proteinuria he was referred
for evaluation. On examination, the patient was well nourished
(weight 46 kg, and height 157 cm) with periorbital edema and blood
pressure140/84 mm Hg. Systemic examination was normal. Urinalysis
showed 2+ albumin, red blood cells and Up/Uc ratio of 0.33. Blood
investigations showed a creatinine of 1.0 mg/dL, albumin 4.2 g/dL
and potassium 5.1 mEq/L. Ultrasonogram of the kidneys showed normal
size kidneys. Renal biopsy showed seven glomeruli of which two were
completely sclerosed and one showed segmental sclerosis and
proliferation. Remaining glomeruli were normal-sized with increase
in mesangial cellularity and thin capillary walls; tubules,
interstitium and blood vessels were unremarkable. Immuno-fluorescence
examination showed mesangial granular deposits of IgA, and C3c and
IgM. A diagnosis of class III IgA nephropathy was made [3]. The
patient received treatment with angiotensin converting enzyme
inhibitors and fish oil supplements without steroids. Later, he
received therapy with an angiotensin receptor blocker. Ten months
later, he was admitted with fever, generalized edema, anemia,
hepatosplenomegaly and a soft systolic murmur. The blood pressure
was 130/80 mm Hg. Investigations showed a serum creatinine level of
0.9 mg/dL, urea 28 mg/dL, uric acid 6.8 mg/dL, sodium 134 mEq/L,
potassium 3.4 mEq/L and albumin 3.9 g/dL. The hemoglobin level was
8.5 g/dL, with leukocytes 237200/cu mm, and differential count of 6%
polymorphs, 5% lymphocytes, 9% eosinophils, 10% basophils, 8% stab
neutrophils, 6% myelocytes, 9% metamyelocytes, 10% promyelocytes,
32% myeloblasts and 5% nucleated red cells; platelets were normal. A
diagnosis of CML with blast crisis was made (Fig 1),
and the patient received intravenous and oral fluids of 3 L /day
along with alkalization of urine and allopurinol. BCR-ABL
translocation assay showed hybrid transcript in leukocytes
suggesting chronic phase of CML. Genomic breakpoint observed at
e14a2 corresponds to p210. The patient was treated with Imatinib 400
mg once a day [4, 5]. After 1 month follow-up, there was no
hepatosplenomegaly, and leukocyte counts and renal functions were
normal.
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Fig.1 Peripheral smear showing
features of chronic myeloid leukemia.
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Discussion
IgA nephropathy is a common chronic primary
glomerular disease, which rarely presents as acute nephritic
syndrome. Systemic diseases with IgA deposits include systemic lupus
erythematosus, Henoch-Schonlein purpura, cystic fibrosis, ankylosing
spondylitis, dermatitis herpetiformis, inflammatory bowel disease,
celiac disease, chronic liver disease, infections like mycoplasma,
leprosy and toxoplasmosis, as well as neoplasms like non-Hodgkin
lymphoma, monoclonal IgA gammopathy and carcinoma of the lung and
colon [1]. Various hypotheses suggested in the pathogenesis of IgA
nephropathy are predisposing genetic factors, IgA immune complex
disease due to abnormal IgA glycosylation and adhesion molecules on
mononuclear cells and lymphocyte subpopulation [1,6,7]. Chromosome
aberrations identified by genome- wide linkage analysis in families
with IgA nephropathy cases is suggested to be predisposing genetic
factor for development of disease [1]. Abnormal galactosylation in
the hinge region of IgA1 subclass results in formation of
circulating immune complex and its deposition in mesangium. These
deposits release cytokines, growth factors and adhesion molecules,
which lead to proliferation of mesangial cells, inflammation and
sclerosis [1,7]. The recognition of B-cell defect and the role of
adhesion molecules/growth factors enables targeting treatment with
bone marrow transplant or neutralizing antibodies [6,7]. Findings
that predict progression to end stage renal disease include heavy
proteinuria, diffuse mesangial proliferation, a high proportion of
glomeruli showing sclerosis, crescents or capsular adhesions, and
the presence of moderate or severe tubulointerstitial changes [8].
There are increasing reports of association between chronic
glomerulo-nephritis and leukemia in adults [9,10]. Renal
infiltration by leukemic cells is rare and presents with abdominal
pain or hematuria with renal biopsy showing presence of abnormal
cells as seen in peripheral blood. The present patient had acute
nephritic syndrome, which was followed three years later by the
occurrence of CML. This association suggests that a B-cell defect
might be involved in the pathogenesis of IgA nephropathy and CML.
Acknowledgement: Histopathology Department of
Apollo Hospitals, Chennai, India for preparation and reporting of
renal biopsy, and Pediatric Hematology and Histopathology
Departments of Mehta Hospitals, Chennai, India for preparation and
reporting of peripheral smear.
Contributors: All the authors were involved
in the case management. MVK, NP and AU were involved in review of
literature and preparation of the manuscript. MVK will act as
guarantor.
Funding: None;Competing interest: None
stated.
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